Empini yekhulu leminyaka phakathi kwesintu nomdlavuza, imvelo ibilokhu ihlinzeka ngemikhondo yokuxazulula inkinga ngezindlela ezingalindelekile. Eminyakeni yamuva nje, i-monosaccharide ebonakala ijwayelekile - iMannose - isiphenduke into egxile emhlabeni wonke ocwaningweni lwesayensi ngenxa yezakhiwo zayo ezihlukile zokulwa nomdlavuza. Le hexose, etholakala kakhulu kuma-cranberries kanye nezithelo ezisawolintshi, inyukile isuka endimeni esekelayo emkhakheni wezokudla okunempilo yaya endimeni ehamba phambili ocwaningweni lwe-tumor metabolism, iveza ubukhulu obusha bezinto zikashukela ekulawuleni impilo. Lesi sihloko sizohlaziya ngokujulile ukuthi i-mannose ilungisa kanjani kabusha indawo yokwelashwa komdlavuza kusuka ezicini ezine: ucwaningo oluyisisekelo, indlela yokwenza, ukuguqulwa komtholampilo kanye namathemba ezimboni.

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Isahluko sokuQala: Ukuguqula Ingqondo: Ukuvuswa Okumelene Nomdlavuza Kwamangqamuzana Amnandi

1.1 I-Paradigm Shift ocwaningweni lweCarbohydrate

Emiqondweni yendabuko, ushukela (ama-carbohydrate) sekuyisikhathi eside kuthathwa ngokuthi "imali yamandla". Ikakhulukazi i-glucose, njengengxenye eyinhloko yokuphefumula kwamaselula, ukuhlobana phakathi kokungajwayelekile kwayo kwe-metabolic nokuthuthukiswa komdlavuza kuboniswe ngokugcwele. Kodwa-ke, ucwaningo oluyimpumelelo olushicilelwe yiCancer Research UK ephephabhukwini elithi Nature ngo-2018 lwabhala kabusha lokhu kulandisa - ithimba labacwaningi likuqinisekisile okokuqala ukuthi i-mannose inganqanda ngokukhetha ukwanda kwamangqamuzana omdlavuza ngokuphazamisa indlela ye-metabolism kashukela yesimila, inomthelela omncane ezicutshini ezijwayelekile. Lokhu kutholakala akugcini nje ngokuchitha inkolelo-mbono yokuthi "bonke ushukela bakhuthaza umdlavuza", kodwa futhi kuvula inkundla yempi entsha yokwelashwa kokungenelela kwe-metabolic.

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1.2 Ukulandeleka Kwebhayoloji KweMannose

Njenge-isomer ye-glucose, i-mannose isatshalaliswa endaweni yamahhala ku-epidermis yezithelo ezifana ne-citrus nama-apula emvelweni, noma ibamba iqhaza ekwakhiweni kolwelwesi lwebhayoloji ngendlela yama-glycoprotein. Emzimbeni womuntu, i-mannose i-phosphorylated ukuze yakhe i-mannose-6-phosphate (M6P), eba i-molecule eyisignali ebalulekile yokuhlunga i-lysosomal enzyme. Ngaphambilini izifundo zomtholampilo zembule indlela yayo ekuvimbeleni izifo ze-urinary tract: ngokubophezela ngokuncintisana kuma-adhesion receptors ama-bacteria e-pathogenic, ivimbela ikoloni yabo ku-urothelium. Lesi sici sidale izinhlobonhlobo zezithako zokudla ezigxile kumannose, kodwa ukutholakala kwamandla awo okulwa nomdlavuza kuye kwaholela ekwenyukeni okukhulu kwenani layo lokusebenza.

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Isahluko Sesibili: Ukuqoshwa Kwesayensi: Okucasula Kathathu KweMannose Against Cancer

2.1 Ukudunwa Kwe-Metabolic: Ukunqamula uchungechunge lokunikezwa "ukulutha koshukela" lwamaseli omdlavuza

Umthelela we-Warburg wamaseli wesimila (asathembele ku-glycolysis ukuze uthole amandla ngisho nasendaweni enomoya-mpilo ocebile) wenza ukuba ukumuncwa kwawo kwe-glucose kufinyelele izikhathi eziyishumi kumaseli avamile. Ithimba laseBrithani lithole ngobuchwepheshe bokulandelela i-isotope ukuthi ngemuva kokuthi i-mannose ingene kumaseli omdlavuza, icutshungulwa yi-hexokinase ukuze yakhe i-M6P futhi iqoqeke ngobuningi ngaphakathi kwamaseli. Le "pseudo-metabolite" ayigcini nje ngokuhlala eziteshini ze-glucose transporter (GLUT), kodwa futhi iqhudelana nokuvimbela umsebenzi we-phosphoglucose isomerase, okuholela ekungabikho kwabaphakathi ababalulekile ku-glycolysis kanye nomjikelezo we-tricarboxylic acid, ekugcineni kubangele inkinga yamandla kumaseli omdlavuza (Umfanekiso 1).

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2.2 I-Epigenetics: Ukulungisa kabusha i-tumor microenvironment

Ucwaningo olwanyatheliswa yi-Fudan University ku-Cell Metabolism ngo-2023 luphinde lwembula ukuthi i-mannose ingahlehlisa ukuphazamiseka kwe-epigenetic kumaseli omdlavuza ngokulawula amazinga e-histone acetylation. Ukuhlola kubonise ukuthi kumangqamuzana omdlavuza we-pancreatic alashwe nge-mannose, izinga le-acetylation lesifunda somgqugquzeli we-oncogene MYC liyancipha, futhi umsebenzi walo wokuloba uvinjelwe kakhulu. Lo mphumela wokuhlelwa kabusha kwe-epigenetic wenza buthaka izici ezihlaselayo nezomile zamangqamuzana e-tumor, okuhlinzeka nge-fulcrum yethiyori yokwakhiwa kwezidakamizwa ezihlanganisiwe ze-epigenetic.

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2.3 I-Immune Synergy: Ukukhipha "Ingubo Engabonakali" ye-PD-L1

Okuphambukisa kakhulu ukuthi ithimba elifanayo lithole ukuthi i-mannose ingakhomba indlela yokuphunyuka kwe-tumor immune system. Ngokuhlaziywa kwe-mass spectrometry, abacwaningi baqinisekisile ukuthi i-mannose ivimbela ukugoqa okulungile kanye nolwelwesi lwasendaweni lweprotheni ye-PD-L1 ngokuphazamisa ukuguqulwa kwayo kwe-N-glycosylation. Iphrotheni ye-PD-L1, elahlekelwa "isambulela sokuzivikela" sochungechunge lukashukela, kungenzeka ukuthi ihlale yonke indawo futhi yonakaliswe, ngaleyo ndlela iqede isignali evimbela kuma-T cell. Kumodeli yegundane le-melanoma, inhlanganisela ye-mannose kanye ne-anti-PD-1 antibody inyuse izinga lokuhlehla kwesimila laya ku-78%, elidlula kude elokwelashwa okukodwa (Umfanekiso 2).

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Isahluko Sesithathu: Ukusuka Elabhorethri kuya Emtholampilo: Indlela Ethuthukile Yemithi Yokuhumusha

3.1 Iziqongo zocwaningo lwangaphambi komtholampilo

Ezivivinyweni eziningi zezilwane, i-mannose ibonise amandla amakhulu okulwa nomdlavuza. Ithimba laseBrithani lingenelele amagundane emodeli yomdlavuza we-pancreatic ngamanzi okuphuza ama-mannose angama-20% futhi lathola ukuthi ukukhula kwevolumu yesimila kubambezeleke ngamaphesenti angama-40, futhi kwakungekho ubuthi obubalulekile besibindi noma izinso. Okujabulisa nakakhulu, lapho isetshenziswa ngokuhambisana ne-gemcitabine, isikhathi sokusinda samagundane sanwetshwa izikhathi ezingu-2.3, okuphakamisa ukubaluleka kwayo kokuzwela ngamakhemikhali. Ukuhlolwa kokuqinisekisa okuzimele esikhungweni somdlavuza we-MD Anderson e-United States kubonise ukuthi i-mannose iphumelela ngokulinganayo ezinhlotsheni zomdlavuza we-refractory ezifana nomdlavuza webele one-triple-negative kanye ne-glioblastoma.

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3.2 Ukuhlola Ngokucophelela kokuhlolwa kwabantu

Ngaphandle kwedatha ye-preclinical ehlaba umxhwele, izivivinyo zabantu zibhekana nezinselele eziyingqayizivele. Ukuhlolwa komtholampilo kweSigaba I (NCT05220739) okwaqalwa ngo-2022 kwaba ngesokuqala ukuhlola ukuphepha kwemannose yomlomo ezigulini ezinamathumba aqinile athuthukile. Idatha yokuqala ibonisa ukuthi iziguli eqenjini le-5g nsuku zonke zinokubekezelela okuhle, futhi amazinga e-DNA yesimila esijikelezayo (ctDNA) kwezinye izimo ehle kakhulu. Kodwa-ke, lapho umthamo ukhuphukela ku-10g, cishe u-15% weziguli waphathwa isifo sohudo esincane, okuphakamisa isidingo sokwandisa uhlobo lomthamo.

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3.3 Izithiyo Zezobuchwepheshe ekuthuthukisweni kwezimboni

Nakuba i-mannose ekhishwe ngokwemvelo iphephile, idinga umthamo ophezulu kakhulu ukuze kufinyelelwe ekugxilweni kokulwa nomdlavuza (okulingana nokudla amakhilogremu angu-5 ama-cranberries nsuku zonke), okuqhubekisele phambili ukuthuthukiswa kobuchwepheshe kubhayoloji yokwenziwa. Njengamanje, i-Escherichia coli eyakhiwe ngofuzo ingakhuphula ukukhiqizwa kwe-mannose izikhathi ezingu-20, kuyilapho i-immobilised enzyme catalysis inciphisa izindleko zokukhiqiza zibe ngaphansi kwama-$50 ngekhilogremu. Ngaphezu kwalokho, ubuchwepheshe be-nano-liposome encapsulation bungakhuphula ukusebenza kahle kokulethwa okuhloswe kwe-tumor ku-80%, kuvule indlela yokuguqulwa komtholampilo.

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Isahluko Sesine Ukungqubuzana Nokuzindla: Imicabango Ebandayo kuMkhosi Wesayensi

4.1 "Inkemba esika-kabili" Umphumela wokungenelela kwe-Metabolic

Kuyaphawuleka ukuthi mannose akuyona panacea. Amanye amangqamuzana omdlavuza aphethe ukuguqulwa kwe-mannose phosphate isomerase (PMI) angaguqula i-mannose-6-phosphate ibe i-fructose-6-phosphate, esikhundleni salokho ethuthukisa ukugeleza kwe-glycolytic. Le nto "yokuphunyuka kwe-metabolic" itholwe cishe ku-7% wamasampuli omdlavuza we-colorectal, okuphakamisa isidingo sokuthuthukisa izimpawu zokuhlola ezizimele.

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4.2 Okungokwemvelo ≠ Iphephile: Ubuciko Bokulawula Umthamo

Nakuba i-mannose igunyazelwe ukusetshenziswa ekudleni njengento ye-GRAS (Ngokujwayelekile Iqashelwa Njengephephile), ubuthi bayo besikhathi eside emithini yokulwa nomdlavuza busadinga ukuthathwa ngokungathi sína. Ukuhlolwa kwezilwane kuthola ukuthi ukuphuza umthamo omkhulu okuqhubekayo kungase kubangele ukuphazamiseka kwezitshalo zamathumbu, ngobuningi bamagciwane athile angosomathuba (njenge-Klebsiella) akhuphuka ngokuphindwe kashumi. Lokhu kudinga ukuthi ucwaningo lwesikhathi esizayo kufanele lulinganisele ukusebenza kahle kokwelapha kanye ne-microecological homeostasis.

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4.3 Umdlalo ophakathi kwe-Commercial Hype kanye ne-Scientific Rationality

Ngomqondo wokuthi "ushukela olwa nomdlavuza" usudumile, abanye abathengisi baye benza ihaba ngemiphumela yokwelapha yemikhiqizo yezempilo ye-mannose. I-FDA yase-United States ikhiphe izincwadi eziyisixwayiso eziya kumabhizinisi amathathu ngokukhuthazwa kwawo ngokungemthetho, igcizelela ukuthi "izithako zokudla azikwazi ukuthatha indawo yokwelashwa kwezidakamizwa." Ososayensi bafuna ukuthi kusungulwe uhlu olugunyaziwe lwemboni ukuze kulawuleke ukulebula nokumakethwa kwemikhiqizo equkethe i-mannose.

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Isiphetho: Isithombe sesikhathi esizayo soguquko olumnandi

Uhambo lokulwa nomdlavuza lwe-mannose alukona nje kuphela ukuhlangana okuphelele kwezipho zemvelo nobuhlakani bomuntu, kodwa futhi luyimodeli yokuqamba okusha kwemikhakha eyahlukene. Kusukela ekuhlelweni kabusha kwe-metabolic kuya ekwakhiweni kabusha kwe-immune microenvironment, kusukela kumashubhu okuhlola elabhorethri kuya ezimbonini zokwenza imithi, lokhu "kuguquguquka okumnandi" kubhala kabusha incwadi yomthetho yokwelashwa komdlavuza. Nakuba kusenezinselelo eziningi ezizayo, kungabonwa kusengaphambili ukuthi isizukulwane esilandelayo sezidakamizwa ezine-glyco esekelwe kumannose singase singenise inkathi entsha yokulwa nomdlavuza. Njengoba nje iMvelo yaphawula: "Lapho isayensi idansa nemvelo, insimbi yosuku lwembubhiso yomdlavuza isivele yakhala."

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